1. Field of the Invention
The present invention relates to methods of preventing or inhibiting the growth of Helicobacter through the use of a composition that comprises a glucosinolate, an isothiocyanate or a derivative or metabolite thereof. The present invention also relates to methods of preventing or treating persistent chronic gastritis, ulcers and/or stomach cancer in subjects at risk for, or in need of treatment thereof.
2. Background of the Invention
Stomach cancer is the second most common form of cancer worldwide. Helicobacter pylori is a microaerophilic, gram-negative bacterium of cosmopolitan distribution that causes persistent chronic gastritis. Carriers of H. pylori (in gastric mucosa) are at 3 to 6 times the risk for developing stomach cancer (gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma) as non-carriers (J. Danesh et al., Cancer Surveys, 33:263-289 (1999); D. Forman et al., Br Med Bull, 54:71-78 (1998); S. Hansen et al., Scand J Gastroenterol, 34:353-360 (1999); J-Q Huang et al., Gastroenterology, 114:1169-1179(1998)). H. pylori causes inflammation of stomach tissue in carriers, resulting in increased blood flow, swelling and irritation. Inflammation of the lower part of the stomach leads to ulcers in about 10% of carriers. Inflammation of the upper part of the stomach leads to impaired acid secretion and ultimate die-off of acid-producing cells and leads to reduced stomach function and ultimately to cancer.
Helicobacter pylori was only first described following its cultivation from human gastric biopsy specimens in 1982 (J R Warren et al., Lancet, (1983), 1:1273-1275; B J Marshall et al., Microbios Lett. (1984), 25:83-88). Since then, as many as 26 related Helicobacter species have been described colonizing the mucosal surfaces of humans and other animals (J D B Schauer, Clin Microbiol Rev, (2001), 14:59-97). These organisms not only colonize gastric tissues of mammals, but are found in the intestinal tract and the liver of birds, as well as in mammals including humans, mice, ferrets, gerbils, dogs and cats. They have been implicated as agents responsible for inflammation, and in malignant transformation in immunocompetent hosts as well as immunocompromised humans and animals. However, H. pylori is now well-documented as one of the most prevalent human pathogens worldwide (R M Genta et al., Virchows Arch, 425:339-347 (1994)), and the causal agent for most gastric and duodenal ulcers, as well as a risk factor for the development of gastric cancer (J Danesh, Cancer Surveys, 33:263-289 (1999)). The human stomach is the only known natural reservoir for H. pylori, although many mammalian species can be infected by related species. Antibiotic therapy aimed at eradication of H. pylori (e.g. amoxycillin and clarithromycin plus the H2 inhibitor omeprazol for 10-14 days) is now recommended for infected patients who have verified peptic ulcerations of the stomach or duodenum or who have gastric mucosa-associated lymphoid tissue lymphomas, and cure rates are on the order of 90% (Helicobacter Foundation, “Treatment of Helicobacter pylori, p. 1-5 (1998)). However, a complex antibiotic therapy as described above may not be available in developing countries, where H. pylori infection rates can be as high as 70% of the population.
Thus a need exists for an economical dietary supplement, food or pharmaceutical that will naturally inhibit the growth and/or infection rates of H. pylori, both in the lumen of the stomach and within gastric epithelial cells where H. pylori may serve as a low-level, chronic reservoir for re-infection. This inhibition of eradication can in turn reduce the incidence of ulcers and stomach cancer or prevent reinfection of H. pylori. 